Genetic Analysis of Protection from Environmental Stress-Induced Degeneration: Characterization of a Loss of Function Drosophila Mutant for the Cytoplasmic RNA Exosome Component, dSKI2

Open Access
Moon, Mackenzie Taylor
Area of Honors:
Bachelor of Science
Document Type:
Thesis Supervisors:
  • Richard W Ordway, Thesis Supervisor
  • Richard W Ordway, Honors Advisor
  • Dr. Stephen Wade Schaeffer, Faculty Reader
  • Drosophila melanogaster
  • neurodegeneration
  • heat shock
  • pele
  • SKI2
  • Ski complex
  • infertility
Given the growing burden of degenerative diseases on human health and healthcare, defining the precise mechanisms that underlie these diseases as well as mechanisms which may mediate protection against cellular degeneration remains a key research objective. Both genetic and environmental factors are known to contribute to the development of degenerative diseases such as Alzheimer’s and Parkinson’s, however the mechanisms mediating environmental contributions are poorly understood. We are investigating these mechanisms using a simple but powerful experimental model of environmental stress-induced degeneration in Drosophila. Previous studies in our laboratory revealed that environmental stress administered to wild-type flies in the form of heat shock (HS) induced a selective loss of flight ability and severe degeneration of flight motor cells. A genetic screen described in this work recovered a new mutant, pele, that demonstrates a marked resistance to degeneration and to the loss of flight motor function. Genetic analysis characterized pele as an allele of dski2, a gene which encodes a required component of the cytoplasmic RNA exosome. Furthermore, this work explores the basis of an interesting infertility phenotype in parallel studies of the pele mutant. We anticipate that our investigation of infertility will converge with genetic analysis of degenerative mechanisms, providing further insight into the molecular mechanisms which operate in pele to confer protection. By identifying mechanisms that confer protection against environmental stress-induced degeneration, we hope to gain insight that can be applied to the development of gene-targeted therapies.